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Trial registered on ANZCTR


Registration number
ACTRN12618000948291
Ethics application status
Approved
Date submitted
31/05/2018
Date registered
5/06/2018
Date last updated
6/09/2019
Date data sharing statement initially provided
13/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A first in human study to evaluate the safety and immune response to a vaccine for the treatment of a respiratory virus, when administered into the arm in healthy adult participants.
Scientific title
A Phase I, first in human (FIH), randomised, double-blind, placebo-controlled, dose-escalation study to evaluate safety, reactogenicity and immunogenicity of the recombinant respiratory syncytial virus vaccines (BARS13) when administered intramuscularly (IM) to healthy adult volunteers.
Secondary ID [1] 295062 0
None
Universal Trial Number (UTN)
U1111-1214-9745
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Respiratory Syncytial Virus Infection 308109 0
Condition category
Condition code
Infection 307148 307148 0 0
Other infectious diseases
Respiratory 307163 307163 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A total of up to 60 eligible participants will be enrolled and randomised in a 4:1 ratio (investigational vaccine versus placebo) to receive one of the following treatments:

• BARS13 low dose (one dose of 10 µg rRSV-G protein/10 µg CsA by IM injection to the deltoid region of one arm, and one dose of placebo [saline/mannitol] by IM injection to the deltoid region of the other arm, given sequentially).
• BARS13 high dose (IM injection of 10 µg rRSV-G protein/10 µg CsA administered to the deltoid region of each arm [one injection of 10 µg rRSV-G protein/10 µg CsA per arm], given sequentially). The high dose is twice the strength of the low dose.
• Placebo (IM injection of saline/mannitol administered to the deltoid region of each arm [one injection per arm], given sequentially).

Dose escalation will be undertaken following one of two vaccination regimens across 4 cohorts (15 participants/cohort):

Cohort 1: low dose IM injection on Day 0 (12 active, 3 placebo); with follow up at 7 days ± 1 day post vaccination and at Day 30 ± 5 days and a final follow up/end of study (EOS) teleconference assessment at Day 60 ± 5 days.

Cohort 2: low dose IM injection on Day 0 and at Day 30 (12 active, 3 placebo) with follow up at 7 days post vaccination (Day 7 ± 1 day and Day 37 ± 1 day) and Day 60 ± 5 days and a final follow up/ EOS teleconference assessment at Day 90 ± 5 days.

Cohort 3: high dose IM injection on Day 0 (12 active, 3 placebo); with follow up at 7 days ± 1 day post vaccination and at Day 30 ± 5 days and a final follow up/end of study (EOS) teleconference assessment at Day 60 ± 5 days.

Cohort 4: high dose IM injection on Day 0 and at Day 30 (12 active, 3 placebo) with follow up at 7 days post vaccination (Day 7 ± 1 day and Day 37 ± 1 day) and Day 60 ± 5 days and a final follow up/ EOS teleconference assessment at Day 90 ± 5 days.

All participants will be observed while in the clinic by the PI and site staff to ensure the safety of participants.
A safety monitoring committee will review safety date following Cohort 1 and following Cohorts 2 and 3. No participant will be a member of more than one cohort.
Intervention code [1] 301395 0
Treatment: Drugs
Comparator / control treatment
Placebo controlled (saline/mannitol)
Control group
Placebo

Outcomes
Primary outcome [1] 306105 0
Composite outcome:
• Incidence and severity of AEs from baseline (Day 0) to the end of the 7-day follow up period after each vaccination. This includes the occurrence of vaccine-related AEs (solicited AEs) as follows:
o Incidence and severity of local reactions (pain, tenderness, erythema, swelling, other e.g. ulceration, scabs, redness, induration, ecchymosis, oedema, itching and paraesthesia) at the site of vaccination assessed by patient reported AEs and diary card

o Incidence and severity of systemic reactions (fatigue, myalgia, malaise, fever, rigors, arthralgia, nausea, diarrhoea, light-headedness, dizziness, hypersensitivity and headache) assessed by patient reported AEs and diary card
Timepoint [1] 306105 0
7 days post vaccination
Primary outcome [2] 306106 0
Occurrence of any AE during a 30-minute post-vaccination safety observation period on Day 0 (all cohorts) and Day 30 (cohorts 2 and 4) assessed by patient reported AEs (eg injection site reactions, allergic reactions or anaphylaxis)
Timepoint [2] 306106 0
30 minutes post vaccination on Day 0 and 30
Primary outcome [3] 306107 0
Composite outcome:
• Occurrence of any AE during a 30-day follow-up period after each vaccination. Any ‘solicited’ AE with onset outside the specified 7 day period of follow-up will be reported as an unsolicited adverse event assessed by patient reported AEs and diary card
• Occurrence of any AE leading to withdrawal during the 30-day follow up period after each vaccination assessed by patient reported AEs and diary card
Timepoint [3] 306107 0
30 days post vaccination
Secondary outcome [1] 347597 0
• Humoral response to BARS13: IgG antibody titers measured by ELISA prior to vaccination (Day 0) and post vaccination at Day 30 (all cohorts) and at Day 60 (cohorts 2 and 4 only) and expressed as follows:
o Corrected post-dose Geometric Mean Titers (GMTs) of IgG antibody against RSV-G
o Post-dose Geometric Mean Fold Rises (GMFRs) from baseline of IgG antibody against RSV-G.
Timepoint [1] 347597 0
Pre-vaccination, 30 day post each vaccination
Secondary outcome [2] 347636 0
Primary outcome:
Occurrence of any Serious Adverse Event (SAE) form baseline (Day 0) to the last visit
Timepoint [2] 347636 0
60 days post last vaccination
Secondary outcome [3] 347637 0
Primary outcome:
Occurrence of any clinical laboratory abnormalities (Toxicity grade > or = 1) form baseline (Day 0) to the last visit
Timepoint [3] 347637 0
60 days post last vaccination
Secondary outcome [4] 347638 0
Primary outcome:
Treatment emergent, clinically significant changes in vital sign (blood pressure, respiratory rate, pulse rate and oral temperature) and physical examination findings s specified intervals after each vaccination
Timepoint [4] 347638 0
30 days post last vaccination

Eligibility
Key inclusion criteria
1. A male or female aged 18-45 years (inclusive) at the time of the first vaccination.
2. Able to communicate effectively with study personnel and is considered reliable, willing, and cooperative in terms of compliance with the protocol requirements.
3. Written informed consent signed prior to undertaking any protocol related procedures.
4. Haematology, clinical chemistry and urinalysis test results not deviating from the normal reference range by age and gender to a clinically relevant extent at screening.
5. Males must be surgically sterile (>30 days since vasectomy with no viable sperm), abstinent or, if engaged in sexual relations with a person of child-bearing potential, the participant and his partner must use an acceptable, highly effective, contraceptive method from screening and for a period of at least 3 months after the last dose of study drug. Acceptable methods of contraception are the use of condoms and an effective contraceptive for the female partner that could include: surgical sterilization (e.g., bilateral tubal ligation), hormonal contraception, or intrauterine contraception/device. The PI is to assess the adequacy of methods of contraception on a case-by-case basis.
6. Women of child-bearing potential (WOCBP) must use highly effective contraceptive measures (failure rate of < 1% per year when used consistently and correctly) throughout the study and intend to continue use of contraception for at least 3 months following the last vaccination. Highly effective contraceptive measures could include: combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone releasing system, bilateral tubal occlusion, vasectomised partner, and sexual abstinence. The PI is to assess the adequacy of methods of contraception on a case-by-case basis.
7. Participant in otherwise general good health based on medical history and physical examination, as determined by the PI.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Presence of clinically significant medical history, unstable chronic or acute disease, or physical, or laboratory findings that, in the opinion of the PI may potentially increase the expected risk of exposure to the investigational vaccine, compromise the safety of the participant, or interfere with any aspect of study conduct or interpretation of results.
2. Body Mass Index (BMI) great than or equal to 40 at screening.
3. Significant infection or other acute illness, including fever over 37.5°C/99.5°F on the day of randomisation.
4. Birthmarks, tattoos, wound or other skin conditions over the deltoid region of both arms that, in the PI’s opinion, could reasonably obscure and interfere with evaluation of local injection site reactions.
5. Inadequate venous access to allow collection of blood samples.
6. Breastfeeding or pregnant as confirmed by a positive serum beta human chorionic gonadotropin (ß-HCG) pregnancy test at screening or positive urine pregnancy test at subsequent clinic visits at time points as delineated in the study schedule.
7. Received any prophylactic or therapeutic vaccine, or investigational drug, within 3 months of first vaccination, or anticipated in the follow up period defined for this study.
8. History of severe allergy (requiring hospital care), severe reaction to any drug or prior vaccination, or any known or suspected allergies or sensitivities to any component of the investigational vaccine or placebo.
9. Immunosuppression caused by disease (such as human immunodeficiency virus [HIV]) or medications, immunosuppressive therapy (such as long-term systemic corticosteroids therapy).
10. History of hepatitis B or hepatitis C infection.
11. History of autoimmune disorder.
12. History of splenectomy or of condition affecting splenic function.
13. History of malignancy of any organ system (other than localised basal cell carcinoma of the skin), treated or untreated, within the past five years, regardless of whether there is evidence of local recurrence or metastases.
14. History of any neurological disorders or seizures.
15. Thrombocytopenia or bleeding disorder contraindicating intramuscular vaccination.
16. Receipt of immunoglobulins or blood products within 3 months of first vaccination.
17. Requirement for antipyretic or analgesic medication on a daily or every other day basis from randomisation through 72 hours after vaccination.
18. History of alcohol or drug abuse or psychiatric disorder that in the opinion of the PI could affect the participants’ safety or compliance with study.
19. Positive urine drug screen at screening, or pre-vaccination for any drug of abuse unless there is an explanation acceptable to the PI (e.g. the participant stated in advance that they consumed a prescription or over the counter product which contained the detected drug) and/or the participant had a negative urine drug screen on retest by the pathology laboratory.
20. A positive alcohol breathalyser test at screening or pre-vaccination.
21. Participant unwilling to abstain from blood donation during the course of the study, and/or participation in any research study involving blood sampling (more than 450 mL /unit of blood), or blood donation to the Australian Red Cross Blood Service (ARCBS) or other blood bank during the 2 months prior to the screening visit

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Since the study is a pilot, without consideration given to formal hypothesis testing, the focus of the statistical analysis will be descriptive and a sample size calculation for statistical power will not be performed.
The following analysis populations will be assessed in the study:
All Participants population: consisting of all enrolled and randomised participants. The All Participants population will be used for presentation of disposition, demographic and baseline data.
Safety population: consisting of all participants who receive any study treatment (BARS13 or placebo). The Safety population will be used to present safety and tolerability data.
Immunogenicity population: consisting of all participants who receive any amount of study treatment (BARS13 or placebo) and who have at least one post-baseline immunological evaluation.
Per Protocol (PP) population: consisting of all participants in the Immunogenicity population who receive all vaccinations with BARS13 or placebo and who complete all study assessments.
All immunogenicity evaluations will be performed on both the Immunogenicity and PP populations.
Study participants with stable asthma who use concomitant medications of asthma inhalers and/or topical corticosteroids are to be excluded from the Immunogenicity PP analysis population.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
16/10/2018
Actual
16/10/2018
Date of last participant enrolment
Anticipated
19/02/2019
Actual
8/03/2019
Date of last data collection
Anticipated
19/06/2019
Actual
2/08/2019
Sample size
Target
60
Accrual to date
Final
60
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 11053 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 22849 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 299644 0
Commercial sector/Industry
Name [1] 299644 0
Advanced Vaccine Laboratories Pty Ltd
Country [1] 299644 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Advanced Vaccine Laboratories Pty Ltd
Address
Suite 2-4
321 Chapel Street,
Prahran,
Victoria 3181
Country
Australia
Secondary sponsor category [1] 298970 0
Commercial sector/Industry
Name [1] 298970 0
Clinical Network Services (CNS) Pty Ltd
Address [1] 298970 0
Level 2 381 MacArthur Avenue Hamilton, Queensland 4007
Country [1] 298970 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300541 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 300541 0
Ethics committee country [1] 300541 0
Australia
Date submitted for ethics approval [1] 300541 0
06/06/2018
Approval date [1] 300541 0
03/07/2018
Ethics approval number [1] 300541 0
Project Number 110/18

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84002 0
Dr Ben Snyder
Address 84002 0
Level 5 Burnet Building AMREP Precinct
89 Commercial Road
Melbourne, VIC 3004
Country 84002 0
Australia
Phone 84002 0
+61 3 9076 8960
Fax 84002 0
Email 84002 0
b.snyder@nucleusnetwork.com.au
Contact person for public queries
Name 84003 0
Ben Snyder
Address 84003 0
Level 5 Burnet Building AMREP Precinct
89 Commercial Road
Melbourne, VIC 3004
Country 84003 0
Australia
Phone 84003 0
+61 3 9076 8960
Fax 84003 0
Email 84003 0
b.snyder@nucleusnetwork.com.au
Contact person for scientific queries
Name 84004 0
Ben Snyder
Address 84004 0
Level 5 Burnet Building AMREP Precinct
89 Commercial Road
Melbourne, VIC 3004
Country 84004 0
Australia
Phone 84004 0
+61 3 9076 8960
Fax 84004 0
Email 84004 0
b.snyder@nucleusnetwork.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Commercially sensitive and confidential information.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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